The present invention relates to the localized delivery of genetic information to target locations within the mammalian body, and more particularly to the delivery of genetic information from biostable materials coated onto medical devices.
The treatment of disease such as vascular disease by local pharmacotherapy presents a means of delivering therapeutic drug doses to target tissues while minimizing systemic side effects. Recently, for example, the local delivery of gene constructs to effect vascular response has gained increased interest. Gene transfection of vascular smooth muscle cells in vivo, however, is often difficult because of the low transfer efficiency attributed in part to inefficient local delivery devices and to the barrier properties of the vessel wall.
As an example of localized delivery of therapeutic agents, in vivo adenoviral gene transfer has been accomplished with the use of site-specific delivery catheters. Because genetic materials are typically in the form of large molecules, however, it has been difficult to engineer biostable delivery materials that can hold the genetic materials during delivery within the body and then release the genetic materials upon reaching a target location. Rather, such delivery is accomplished by incorporating the genetic information into a biodegradable medical device or coating, whereby the genetic information is released as the biodegradable material disintegrates while in the body. The use of biodegradable materials within the body, however, often results in adverse interactions with tissue and the resultant inflammation thereof. Further, biodegradable materials are generally characterized by a short shelf-life because they typically degrade upon exposure to the ambient atmosphere.
In one aspect, the present invention relates to a system for the localized delivery of genetic information to a target location within a mammalian body. In one embodiment, the system comprises a medical device insertable into the body and a biostable coating over at least part of the medical device. Genetic information is incorporated into the biostable coating before the medical device is placed into the body, and is released from the biostable coating at a target location within the body.
In another aspect, the present invention relates to method for the localized delivery of genetic information to a target location within a mammalian body. In one embodiment, the method includes the steps of providing a medical device insertable into the body, coating at least a portion of the medical device with a biostable material, incorporating the genetic information into the biostable material, and placing the medical device at the target location. The genetic information is released from the biostable material at the target location.
In another aspect, the present invention relates to medical devices at least partially covered with a biostable coating that facilitates the localized delivery of genetic information.
One advantage of the present invention is that it provides biostable coatings for medical devices, and methods of making such coatings, that are suitable for holding and releasing genetic information.
Another advantage of the present invention is that it provides for the localized delivery of genetic information from biostable materials, thus avoiding the potential problems of delivery from biodegradable polymers.
Yet another advantage of the present invention is that it provides for the localized delivery of genetic information in a controlled and reproducible manner.